Summary The plasma concentrations of protein S, protein C and C4b-binding protein (C4BP) were analysed during pregnancy, in the postpartum period and in women using oral contraceptives. Free protein S. measured after precipitation of the C4BP-protein S complexes with 5% PEG 6000, was found to be 8.3 mg/l in the control group, which represents 36.3% of the total plasma protein S content (average 23.5 mg/l). The concentration of protein S was significantly decreased during pregnancy, the lowest levels occurring in the second trimester (14.8 mg/1). The values returned to normal within a few days after delivery. The concentration of free protein S was also decreased, down to an average of 3.7 mg/l at delivery, and did not return to normal within the first week postpartum. The mean concentration of protein S in women using oral contraceptives decreased to 17.7 mg/l and the free fraction went down to 6.6 mg/l. Unlike that of protein S, the plasma concentration of protein C increased during pregnancy, reaching a maximum of 135% in the second trimester. Also, it was significantly higher in the postpartum period and in women using oral contraceptives, than in controls. The level of C4BP was increased throughout pregnancy, with a maximum of 143.4% at delivery. These changes in the plasma levels of proteins C and S during pregnancy indicate that the two proteins differ in the regulation of their synthesis. The major decrease in the level of free protein S may predispose to thrombotic episodes during pregnancy, whereas the increased level of protein C may have the reverse effect. These results indicate the importance of taking into account the normal changes in the plasma levels of protein C and S during pregnancy and the use of oral contraceptives, when evaluating patients with increased risk of thromboembolic disease.